School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University, China.
FEBS Lett. 2019 Jun;593(12):1372-1380. doi: 10.1002/1873-3468.13441. Epub 2019 May 30.
Here, a complete set of recombinant fission yeast strains that coexpress each of the 57 human cytochrome P450 (CYP) enzymes together with their natural human electron transfer partner(s) was cloned. This strain collection was tested with two luminogenic probe substrates, and 31 human CYPs (including the orphan enzymes CYP2A7, CYP4A22 and CYP20A1) were found to metabolize at least one of these. Since other substrates are known for the remaining enzymes, all human CYPs are now shown to be active. Interestingly, CYP5A1 was found for the first time to work on a substrate other than prostaglandin H , and, moreover, to catalyze an aliphatic hydroxylation reaction that consumes molecular oxygen. Also, the ability of CYP11A1 to catalyze an aryl hydroxylation is another unexpected result.
在这里，构建了一套完整的重组裂殖酵母菌株，这些菌株共表达了 57 个人类细胞色素 P450（CYP）酶及其天然的人类电子转移伙伴。使用两种发光探针底物对该菌株进行了测试，发现 31 种人类 CYP（包括孤儿酶 CYP2A7、CYP4A22 和 CYP20A1）至少能代谢其中一种底物。由于其他酶已知有其他底物，现在所有人类 CYP 都被证明是有活性的。有趣的是，首次发现 CYP5A1 可以作用于除前列腺素 H2 以外的底物，并催化消耗分子氧的脂肪族羟化反应。此外，CYP11A1 催化芳基羟化的能力也是另一个意外的结果。
